DESCRIPTION: (Applicant's Abstract) Investigations of pharmacotherapies for cocaine dependence have tended to focus upon traditional medications, such as those effecting dopamine or norepinephrine systems. Fewer clinical trials have examined the efficacy of less traditional pharmacotherapeutic agents such as natural dietary compounds that might correct homeostatic imbalances associated with cocaine use. This is a proposal to test the efficacy of tryptophan in a relapse prevention model for cocaine dependence.Tryptophan, a naturally-occurring dietary constituent, is the metabolic precursor for serotonin. Preclinical evidence demonstrates tryptophan significantly attenuates stimulant self-administration, but there are no clinical investigations of tryptophan as a relapse prevention agent in the treatment of cocaine dependence. Two concurrent double-blind, placebo-controlled outpatient clinical trials will be conducted. One will enroll opiate-dependent patients maintained on methadone who abuse cocaine, and the other will enroll non-opiate dependent cocaine abusers. It is important to examine tryptophan's efficacy in both populations, because the populations are likely to differ on treatment retention, on pretreatment characteristics, and possibly on response to treatment. While novel pharmacotherapies may help drug abusers abstain, they are not likely to provide the motivation or skills necessary to abstain. For this reason, this project will examine the interaction between tryptophan treatment and a voucher incentive behavior therapy which has previously been shown highly effective for treating cocaine abusers. It is anticipated the behavioral incentive intervention will, by promoting abstinence and treatment retention, will provide optimal conditions for observing tryptophan's effects. Thus, these studies will: 1) Determine whether tryptophan compared to placebo influences relapse to use of cocaine and HIV risk behavior following a brief residential stay that ensures initial abstinence; 2) Examine in a 2x2 design the interaction between tryptophan treatment and a behavioral incentive therapy that provides external incentives to remain drug-free; 3) Compare the effectiveness of the treatments in two separate important populations of cocaine abusers, those who are concurrently dependent upon opioids and are enrolled in methadone maintenance treatment and those who abuse primarily cocaine and are not concurrently opioid dependent; 4) Determine whether tryptophan compared to placebo influences effects of cocaine or self-reported craving for cocaine; 5) Identify patient characteristics associated with positive clinical outcome; 6) Identify patient characteristics associated with differential response to specific treatments or treatment combinations. Overall, this project will provide valuable new information about the ability of a novel, safe, and naturally occurring substance--tryptophan--to decrease the likelihood of relapse to cocaine, in the context of a promising behavioral treatment intervention.